We are a group of 13 multi-disciplinary investigators representing ten departments at the University of California, Irvine with 9 federally funded research projects impacted by this request for instrumentation. We are seeking funds for a Zeiss LSM 51 0 META NLO multi-photon microscope to be housed and supported within the well-established NIH-NCRR Biomedical Technology Resource Center (P41-RR01192, Laser Microbeam and Medical Program, LAMMP) at the Beckman Laser Institute. The LAMMP facility is dedicated to defining and understanding broad issues related to the use of light as a tool to selectively perturb, monitor, and image physiology in cells and tissues. There is an urgent need for a commercial, user-friendly confocal/multi-photon microscope to be housed and managed within our NIH resource. All of the proposed as pilot/feasibility studies using a non-commercial, home-built multi-photon excitation laser scanning system and/or a 14-year-old LSM 410 confocal system. These projects have expanded in scope, and now have extramural federal support that, in turn, requires frequent and often heavy use of laser scanning microscopy. In order to adequately accommodate the maturation of these innovative studies, we are requesting funds to purchase a Zeiss META instrument. This platform ideally accommodates our needs, which range from low-light-level endogenous signal detection of both fluorescence and second harmonic generation (SHG) in tissues to cellular FRET-based imaging. Although LAMMP facilities include multi-photon and confocal microscopy, these instruments are custom-built, low-throughput devices optimized for special needs and pilot/feasibility data. Consequently, continued progress for these NIH-funded investigators is hampered without access to a commercial-grade instrument. It is expected that the requested instrumentation will have a significant overall benefit to the UCI research community and beyond based on the existing strong impact of the LAMMP and its dissemination of new discoveries to colleagues and collaborators. [unreadable] [unreadable] [unreadable]